2713-34-0

Basic information

• Product Name: 3,5-Difluorophenol
• Synonyms: 3,5-DIFLUOROPHENOL;Phenol,3,5-difluoro-;3,5-Difluorophenol,98+%;3,5-Difluorophenol 99%;3,5-Difluorophenol99%;3,5-Diflourophenol;3,5-Difluorophenol, 99% 1GR;3, 5 - two fluorine phenol
• CAS NO: 2713-34-0
• Molecular Formula: C₆H₄F₂O
• Molecular Weight: 130.09
• EINECS: -0
• Product Categories: Fluorobenzene Series;Aromatic Phenols;Fluorobenzene;Phenol&Thiophenol&Mercaptan;Fluorophenols;Organic Building Blocks;Oxygen Compounds;Phenols;Heterocyclic Acids
• Mol File: 2713-34-0.mol
• Article Data: 10

Chemical Properties

• Melting Point: 54-57 °C(lit.)
• Boiling Point: 65-68°C 1mm
• Flash Point: 159 °F
• Appearance: White to beige/Crystals
• Density: 1.2483 (estimate)
• Vapor Pressure: 1.11E-06mmHg at 25°C
• Refractive Index: 1.589
• Storage Temp.: Flammables area
• Solubility: ethanol: soluble50, clear, colorless to faint yellow or tan (mg/
• PKA: 7.97±0.10(Predicted)
• BRN: 2078616
• CAS DataBase Reference: 3,5-Difluorophenol(CAS DataBase Reference)
• NIST Chemistry Reference: 3,5-Difluorophenol(2713-34-0)
• EPA Substance Registry System: 3,5-Difluorophenol(2713-34-0)

Safety Data

• Hazard Codes: Xn,Xi,C,F
• Statements: 20/21/22-36/37/38-34-11
• Safety Statements: 26-36-45-36/37/39-16
• RIDADR: UN 1325 4.1/PG 2
• WGK Germany: 3
• HazardClass: 6.1
• PackingGroup: III
• Hazardous Substances Data: 2713-34-0(Hazardous Substances Data)

Usage

Chemical Properties

white to beige crystals

InChI:InChI=1/C15H14FNO2/c16-13-9-5-4-8-12(13)14(15(18)19)17-10-11-6-2-1-3-7-11/h1-9,14,17H,10H2,(H,18,19)

Synthetic route

2,4,6-trifluorobenzoic acid (28314-80-9) → 3,5-difluorophenol (2713-34-0)

Conditions	Yield
With potassium phosphate In tert-butyl methyl ether; water at 100 - 125℃; for 35h; Reagent/catalyst; Temperature; Solvent; Sealed tube;	96.1%
With water; potassium hydroxide at 90 - 135℃; for 35h; Sealed tube;	95.1%

3,5-difluorophenylboronic acid (156545-07-2) → 3,5-difluorophenol (2713-34-0)

Conditions	Yield
With dihydrogen peroxide; iodine In dichloromethane at 20℃; for 0.666667h; Solvent;	84.9%
With water at 20℃; for 20h;	50 %Chromat.

3,5-difluorobromobenzene (461-96-1) → 3,5-difluorophenol (2713-34-0)

Conditions	Yield
With sulfolane; potassium hydroxide In water at 130℃; under 6000.6 Torr; for 8h; Inert atmosphere; Autoclave;	80.8%

3,5-difluoro-1-(diethoxymethylsilyl)benzene (40161-50-0) → 3,5-difluorophenol (2713-34-0)

Conditions	Yield
With potassium fluoride; dihydrogen peroxide In ethanol for 18h; Heating;	70%

1,3,5-trifluorobenzene (372-38-3) → 3,5-difluorophenol (2713-34-0)

Conditions	Yield
With potassium hydroxide In dimethyl sulfoxide at 132 - 134℃; for 1h;	40%

3,5-difluoroaniline (372-39-4) → 3,5-difluorophenol (2713-34-0)

1,3,5-trifluorobenzene (372-38-3) → 2,2’,4,4’,6,6’-hexafluorobiphenyl (41860-46-2) + 3,5-difluorophenol (2713-34-0) + 2,4,6,2',6'-pentafluoro-biphenyl + 2,4-difluoro-6-(2,4,6-trifluoro-phenoxy)-benzene-1,3-diol

Conditions	Yield
In water pH=5; Kinetics; Quantum yield; Oxidation; Photolysis; 254 nm;

1,3,5-trifluorobenzene (372-38-3) → 3,5-difluorophenol (2713-34-0) + 2,4,6-trifluorophenol (2268-17-9) + 4,6-difluoro-cyclohexa-2,5-diene-1,2-diol + 5'-fluoro-biphenyl-3,5,3'-triol

Conditions	Yield
With dihydrogen peroxide; oxygen In water pH=5; Kinetics; Oxidation; Photolysis; 254 nm;

1,3,5-trifluorobenzene (372-38-3) → 3,5-difluorophenol (2713-34-0) + 3,5-difluoro-cyclohexa-1,5-diene-1,4-diol + 2-fluoro-6-hydroxy-[1,4]benzoquinone + 3-fluoro-2,5-dihydroxy-[1,4]benzoquinone

Conditions	Yield
With dihydrogen peroxide In water pH=5; Kinetics; Oxidation; Photolysis; 254 nm;

1,3,5-trifluorobenzene (372-38-3) → 3,5-difluorophenol (2713-34-0) + 2,4,6-trifluorophenol (2268-17-9)

Conditions	Yield
With dihydrogen peroxide In acetonitrile at 60℃; for 15h; Catalytic behavior;

3,4,5-trifluoro aniline (163733-96-8) → 3,5-difluorophenol (2713-34-0)

Conditions	Yield
Stage #1: 3,4,5-trifluoro aniline With sulfuric acid; sodium nitrite at 20 - 55℃; Stage #2: With dichloromethane; hypophosphorous acid at 20 - 55℃; for 0.5h;

2,4,6-trifluoro-3,5-dichlorobenzonitrile (31881-89-7) → 3,5-difluorophenol (2713-34-0)

Conditions	Yield
Multi-step reaction with 3 steps 1: palladium 10% on activated carbon; hydrogen; magnesium oxide / water / 10 h / 80 - 85 °C / 6000.6 - 6750.68 Torr 2: palladium 10% on activated carbon; hydrogen; magnesium oxide / water / 10 h / 80 - 85 °C / 6000.6 - 6750.68 Torr 3: potassium phosphate / water; tert-butyl methyl ether / 35 h / 100 - 125 °C / Sealed tube View Scheme

2,4,6-trifluoro-3,5-dichlorobenzoic acid (13656-36-5) → 3,5-difluorophenol (2713-34-0)

Conditions	Yield
Multi-step reaction with 2 steps 1: palladium 10% on activated carbon; hydrogen; magnesium oxide / water / 10 h / 80 - 85 °C / 6000.6 - 6750.68 Torr 2: potassium phosphate / water; tert-butyl methyl ether / 35 h / 100 - 125 °C / Sealed tube View Scheme

pentachlorobenzonitrile (20925-85-3) → 3,5-difluorophenol (2713-34-0)

Conditions

Yield

Multi-step reaction with 4 steps 1: potassium fluoride; tetraphenylphosphonium bromide / 20 h / 200 - 210 °C 2: palladium 10% on activated carbon; hydrogen; magnesium oxide / water / 10 h / 80 - 85 °C / 6000.6 - 6750.68 Torr 3: palladium 10% on activated carbon; hydrogen; magnesium oxide / water / 10 h / 80 - 85 °C / 6000.6 - 6750.68 Torr 4: potassium phosphate / water; tert-butyl methyl ether / 35 h / 100 - 125 °C / Sealed tube View Scheme

3,5-difluorophenol (2713-34-0) + methyl iodide (74-88-4) → 3,5-difluoroanisol (93343-10-3)

Conditions	Yield
With potassium carbonate In acetone at 40℃; for 5h;	100%
With potassium carbonate In acetone at 60℃; for 18h;	80%
With potassium carbonate In acetone at 60℃; for 18h;	80%
With hydrogenchloride In tetrahydrofuran

3,5-difluorophenol (2713-34-0) + tert-butylchlorodiphenylsilane (58479-61-1) → (tert-butyl)(3,5-difluorophenoxy)diphenylsilane (701266-25-3)

Conditions	Yield
With 1H-imidazole In dichloromethane at 0℃; for 3.75h;	100%

3,5-difluorophenol (2713-34-0) + aniline (62-53-3) → 3,5-difluoro-4-(phenyldiazenyl)phenol (663602-53-7)

Conditions	Yield
Stage #1: aniline With hydrogenchloride; sodium nitrite In water at 0 - 5℃; Stage #2: With aminosulfonic acid In water Stage #3: 3,5-difluorophenol With hydrogenchloride; sodium hydroxide more than 3 stages;	100%

3,5-difluorophenol (2713-34-0) + 1-chloro-3-hydroxypropane (627-30-5) → 3-(3,5-difluorophenoxy)propan-1-ol

Conditions	Yield
With sodium hydride In N,N-dimethyl-formamide at 0 - 80℃; Large scale;	100%

formaldehyd (50-00-0) + 3,5-difluorophenol (2713-34-0) → 2,4-difluoro-6-hydroxy-benzaldehyde (136516-64-8)

Conditions	Yield
Stage #1: 3,5-difluorophenol With triethylamine; magnesium chloride In acetonitrile at 20℃; Inert atmosphere; Stage #2: formaldehyd In acetonitrile at 20 - 80℃; Inert atmosphere; Stage #3: With hydrogenchloride; water In acetonitrile	100%
With triethylamine; magnesium chloride In acetonitrile at 60℃; for 16h;	82%
With triethylamine; magnesium chloride In acetonitrile at 60℃; for 16h;	82%
With triethylamine; magnesium chloride In acetonitrile at 60℃; for 14h;

3,5-difluorophenol (2713-34-0) + cyclopropylcarbinyl bromide (7051-34-5) → 1-(cyclopropylmethoxy)-3,5-difluorobenzene (1369905-00-9)

Conditions	Yield
With potassium carbonate In N,N-dimethyl-formamide at 20℃;	100%
With potassium carbonate In N,N-dimethyl-formamide at 80℃; for 16h;	90%

2-methyl-1,2-epoxypropane (558-30-5) + 3,5-difluorophenol (2713-34-0) → 1-(3,5-difluorophenoxy)-2-methylpropan-2-ol (1340190-63-7)

Conditions	Yield
With potassium carbonate In N,N-dimethyl-formamide at 150℃; for 0.5h; Microwave irradiation;	100%
With sodium dihydrogenphosphate; water; potassium carbonate In acetonitrile at 140℃; for 6h; steel bomb;	79%

3,5-difluorophenol (2713-34-0) + methanesulfonyl chloride (124-63-0) → 3,5-difluorophenyl methanesulfonate (1149745-39-0)

Conditions	Yield
With triethylamine In ethyl acetate at 0 - 20℃; for 0.166667h; Green chemistry;	99%
With pyridine In dichloromethane at 0 - 20℃; Inert atmosphere;	81%

3,5-difluorophenol (2713-34-0) + 3,4-bis(4-methoxyphenyl)-6-chloropyridazine (67820-94-4) → 3,4-bis(4-methoxyphenyl)-6-(3,5-difluorophenoxy)pyridazine

Conditions	Yield
With potassium carbonate In N,N-dimethyl-formamide at 150℃; for 6h;	98%
at 150℃; for 6h;	98%

5,5a-didehydro-2,3-O-[(2R,3R)-2,3-dimethoxybutane-2,3-diyl]-4,6-O-isopropylidene-5a-carba-β-D-xylohexopyranose (1039643-44-1) + 3,5-difluorophenol (2713-34-0) → C22H28F2O7

Conditions	Yield
Stage #1: 5,5a-didehydro-2,3-O-[(2R,3R)-2,3-dimethoxybutane-2,3-diyl]-4,6-O-isopropylidene-5a-carba-β-D-xylohexopyranose; 3,5-difluorophenol With triphenylphosphine In tetrahydrofuran at 0℃; for 0.333333h; Inert atmosphere; Stage #2: With di-isopropyl azodicarboxylate In tetrahydrofuran at 20℃; for 24h; Inert atmosphere;	97%

3,5-difluorophenol (2713-34-0) + 4-Fluorobenzyl bromide (459-46-1) → 3,5-difluoro-(4-fluoro-benzyloxy)-benzene (636795-71-6)

Conditions	Yield
With potassium carbonate In diethyl ether; acetone	96%
With potassium carbonate In acetone for 6h; Heating / reflux;	96%

3,5-difluorophenol (2713-34-0) + p-toluenesulfonyl chloride (98-59-9) → 3,5-difluorophenyl tosylate

Conditions	Yield
With potassium carbonate In tetrahydrofuran; water at 0 - 20℃; for 2h; Green chemistry;	96%

3,5-difluorophenol (2713-34-0) + N,N-diethylcarbamyl chloride (88-10-8) → O-3,5-difluorophenyl N,N-diethylcarbamate

Conditions	Yield
Stage #1: 3,5-difluorophenol With sodium hydroxide In tetrahydrofuran for 0.166667h; Stage #2: N,N-diethylcarbamyl chloride In tetrahydrofuran at 20℃; for 24h;	96%

2-methoxy-ethanol (109-86-4) + 3,5-difluorophenol (2713-34-0) → 1,3-difluoro-5-(2-methoxyethoxy)benzene (1355011-33-4)

Conditions	Yield
With di-isopropyl azodicarboxylate; triphenylphosphine In tetrahydrofuran at 20℃; for 18h;	95%
With di-isopropyl azodicarboxylate; triphenylphosphine In tetrahydrofuran at 20℃; for 18h;	95%
With di-isopropyl azodicarboxylate; triphenylphosphine In tetrahydrofuran at 20℃; for 18h;	95%

1-bromo-butane (109-65-9) + 3,5-difluorophenol (2713-34-0) → 1-butoxy-3,5-difluorobenzene (123843-64-1)

Conditions	Yield
With potassium carbonate In N,N-dimethyl-formamide at 80℃; for 2h;	94%
With potassium carbonate In acetone for 24h; Heating;	90%

3,5-difluorophenol (2713-34-0) + Isopropyl isocyanate (1795-48-8) → 3,5-difluorophenyl isopropylcarbamate (899427-17-9)

Conditions	Yield
	94%

3,5-difluorophenol (2713-34-0) + tert-butyl 3-hydroxyazetidine-1-carboxylate (141699-55-0) → tert-butyl 3-(3,5-d ifluorophenoxy)azetidine-1-carboxylate

Conditions	Yield
With di-isopropyl azodicarboxylate; triphenylphosphine In tetrahydrofuran at 0 - 60℃; for 48h;	94%
With di-isopropyl azodicarboxylate; triphenylphosphine In dichloromethane at 0 - 20℃; for 18h;

3,5-difluorophenol (2713-34-0) + 5-fluoro-2-nitrobenzonitrile (50594-78-0) → 5-(3,5-difluoro-phenoxy)-2-nitro-benzonitrile (1231250-71-7)

Conditions	Yield
With caesium carbonate In N,N-dimethyl-formamide at 20℃; for 1h;	93%

3,5-difluorophenol (2713-34-0) + 5-bromo-2-fluorobenzaldehyde (93777-26-5) → C13H7BrF2O2

Conditions	Yield
With caesium carbonate In N,N-dimethyl acetamide at 80℃; for 1.5h; Inert atmosphere;	93%

3,5-difluorophenol (2713-34-0) + p-aminoethylbenzoate (94-09-7) → 2,6-difluoro-4-hydroxyazobenzene-4'-carboxylic acid

Conditions	Yield
Stage #1: p-aminoethylbenzoate With sulfuric acid; sodium nitrite In water; acetic acid at 5℃; for 0.5h; Stage #2: 3,5-difluorophenol With sodium hydroxide In water at 5℃; Stage #3: With hydrogenchloride In water	92%

3,5-difluorophenol (2713-34-0) + 2-Chloro-2-oxo-1,3,2-dioxaphospholane (6609-64-9) → C8H7F2O4P

Conditions	Yield
In dichloromethane at 0 - 20℃; for 12h;	92%

3,5-difluorophenol (2713-34-0) + 2-chloro-1,3,2-dioxaphospholan (822-39-9) → 2-(3,5-difluorophenoxy)-1,3,2-dioxaphospholane

Conditions	Yield
Stage #1: 3,5-difluorophenol In dichloromethane at 20℃; for 0.5h; Stage #2: 2-chloro-1,3,2-dioxaphospholan In dichloromethane at 0 - 20℃; for 12h;	92%

3,5-difluorophenol (2713-34-0) + tert-butyldimethylsilyl chloride (18162-48-6) → tert-butyl (3,5-difluorophenoxy)dimethylsilane (917827-99-7)

Conditions	Yield
With 1H-imidazole In N,N-dimethyl-formamide at 0 - 20℃; for 0.333333h;	91%
Stage #1: 3,5-difluorophenol With 1H-imidazole In N,N-dimethyl-formamide at 0℃; for 0.166667h; Stage #2: tert-butyldimethylsilyl chloride In N,N-dimethyl-formamide; toluene at 20℃; for 1h;	88.7%
With 1H-imidazole In N,N-dimethyl-formamide at 0℃; for 3h;	73%

5,6-anhydro-2,3-dideoxy-2-methyl-D-glucono-1,4-lactone (1067648-52-5) + 3,5-difluorophenol (2713-34-0) → C13H14F2O4 (1067648-53-6)

Conditions	Yield
With potassium carbonate In N,N-dimethyl-formamide at 110℃; for 4h;	91%

3,5-difluorophenol (2713-34-0) + 3,5-dibromo-1-(2,2-difluoroethyl)-1H-1,2,4-triazole → 3-bromo-1-(2,2-difluoroethyl)-5-(3,5-difluorophenoxy)-1H-1,2,4-triazole

Conditions	Yield
With potassium carbonate In N,N-dimethyl-formamide at 110℃; for 20h; Sealed tube;	91%

ethyl bromide (74-96-4) + 3,5-difluorophenol (2713-34-0) → 3,5-difluorophenyl ethyl ether (144891-25-8)

Conditions	Yield
With trimethylbenzylammonium bromide; sodium hydroxide In water; N,N-dimethyl-formamide; toluene at 30℃; Reflux; Industrial scale;	90.7%

Tetrahydro-pyran-4-ol (2081-44-9) + 3,5-difluorophenol (2713-34-0) → 4-(3,5-difluorophenoxy)tetrahydro-2H-pyran (1395282-21-9)

Conditions	Yield
With di-isopropyl azodicarboxylate; triphenylphosphine In tetrahydrofuran at 0 - 20℃;	90%
With di-isopropyl azodicarboxylate; triphenylphosphine In tetrahydrofuran at 20℃;	90%
With di-isopropyl azodicarboxylate; triphenylphosphine In tetrahydrofuran at 20℃;	90%

3,5-difluorophenol (2713-34-0) + C31H28Br4O3 → C55H40F8O7

Conditions	Yield
With potassium carbonate In N,N-dimethyl-formamide at 60℃; for 6h; Inert atmosphere; Schlenk technique;	90%

3,5-difluorophenol (2713-34-0) + benzyl chloride (100-44-7) → 1-benzyloxy-3,5-difluorobenzene (176175-97-6)

Conditions	Yield
With sodium hydroxide In ethanol at 100℃; for 1h;	89%

Upstream product

• 372-39-4 3,5-difluoroaniline 
• 372-38-3 1,3,5-trifluorobenzene 
• 20925-85-3 pentachlorobenzonitrile 
• 13656-36-5 3,5-dichloro-2,4,6-trifluorobenzoic acid 
• 31881-89-7 3,5-dichloro-2,4,6-trifluorobenzonitrile 
• 28314-80-9 2,4,6-trifluorobenzoic acid 
• 163733-96-8 3,4,5-trifluoro aniline 
• 461-96-1 3,5-difluorobromobenzene 
• 156545-07-2 3,5-difluorophenylboronic acid 
• 40161-50-0 3,5-difluoro-1-(diethoxymethylsilyl)benzene 

Downstream Products

• 370-02-5 3,5-Difluorophenoxyacetic acid 
• 123843-64-1 1-butoxy-3,5-difluorobenzene 
• 84944-93-4 3',5'-difluorophenyl 3,3-dimethylacrylate 
• 174213-33-3 (S)-tert-butyl 2-(3,5-difluorophenoxymethyl)pyrrolidine-1-carboxylate 
• 182756-57-6 2,6-Difluoro-l-tyrosine 
• 93343-10-3 3,5-difluoroanisol 
• 899427-17-9 (3,5-difluorophenyl) N-isopropylcarbamate 
• 886748-35-2 2,3',4,4',6-pentabromo-3,5-difluorodiphenyl ether 
• 214917-68-7 2,6-difluoro-4-hydroxybenzoic acid 
• 189283-54-3 4,6-difluoro-2-hydroxybenzoic acid 
• 749230-46-4 [2,6-difluoro-4-(methoxymethoxy)phenyl]trimethylsilane 
• 151414-47-0 2,6-difluoro-4-methoxybenzenamine 
• 123843-65-2 2,6-difluoro-4-methoxybenzoic acid 

Relevant articles and documents

Synthesis method of 3, 5-difluorophenol

The invention discloses a synthetic method of 3, 5-difluorophenol, and belongs to the technical field of chemical synthesis. According to the method, 3,5-difluorophenolate is obtained through a one-pot reaction of 2,4,6-trifluorobenzoic acid in a solvent under the action of alkali, 3,5-difluorophenol is obtained after acid regulation and dissociation, and the method has the advantages of cheap and easily available raw materials, short synthesis steps, simple operation, mild reaction conditions, high synthesis yield, good product quality, suitability for industrial production and the like. According to the method, cheap and easily available pentachloronitrile is taken as a raw material, 2, 4, 6-trifluoro-3, 5-dichlorobenzonitrile is obtained through a fluorination reaction, 2, 4, 6-trifluoro-3, 5-dichlorobenzoic acid is obtained through a hydrolysis reaction, and finally, the raw material 2, 4, 6-trifluoro-3, 5-dichlorobenzoic acid is synthesized through a selective dechlorination reaction, so that simple, cheap and efficient preparation of the raw material 2, 4, 6-trifluorobenzoic acid is realized, and the industrial application value of the synthesis process is improved.

Preparation method of 3, 5-difluorophenol

The invention provides a 3, 5-difluorophenol preparation method, which comprises the steps of S1, dissolving 3, 5-difluorobromobenzene in an organic solvent under inert gas protection, adding a bromine pulling agent to carry out a bromine pulling reaction, adding boric acid, filtering, and drying under reduced pressure to obtain 3, 5-difluorophenylboronic acid, and S2, dissolving the 3, 5-difluorophenylboronic acid, and adding an oxidizing agent and a catalyst to obtain the 3, 5-difluorophenol. The 3, 5-difluorophenol preparation method provided by the invention has the advantages of short steps and high yield, and is suitable for industrial production.

A synthetic phenol method of multi-fluoro compounds (by machine translation)

A synthetic phenol method of multi-fluoro compounds, Chinese the solvent, the compound (I) under the action of the catalyst, the reaction temperature 100-180°C, the reaction pressure of 0.3-2.0 MPa, the reaction time 6-12h react under, and then the step (a) in the reaction materials of the formula (II) compound of a post-processing, the process yield can be up to 80% or more, is far higher than the yield of the process the obtained in the past, to achieve product purity 99.5% or more, good color appearance, with mild reaction conditions, high yield, low cost and environment-friendly and the like. (by machine translation)